UT Southwestern Prostate Disease Center investigators have worked together for more than a decade to study the pathogenesis of benign prostatic hyperplasia (BPH) from basic, translational and clinical research prospectives. Our investigators provided the major leadership for the design, supervision and conduct of the NIDDKK-funded MTOPS trial. Furthermore, the group has developed a substantial amount of preliminary data demonstrating the role of several biomarkers in the progression of BPH. Based upon this preliminary evidence, we propose to specifically validate the following biomarkers (or biomarker families) as markers of BPH progression: the prostatic smooth muscle contractile protein phenotype, prostatic alpha-2 macroglobulin, and type 2 5a-reductase. Further assay optimization will be performed with these three biomarkers using the UT Southwestern NIDDK-funded George W. O'Brien Tissue Repository, which contains more than 600 BPH samples and appropriate controls. After assay validation, we propose to test these three markers in the carefully phenotyped MTOPS tissue bank, where detailed correlation with prostate size, growth rate, symptomatic progression and response to therapy can be performed. Furthermore, we propose to explore the potential role of a unique signaling pathway (DOC-2) we believe is an important marker for stem cell proliferation in the prostate, as well as the potential role of telomerase expression in BPH progression in the development of prostatic cancer.